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Biomedical subjects

Kalifa Bojang

Publications and source records attributed to Kalifa Bojang.

6 recordsLinked to original sources
PubMed2004

A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults.

BACKGROUND: Many malaria vaccines are currently in development, although very few have been evaluated for efficacy in the field. Plasmodium falciparum multiple epitope (ME)- thrombospondin-related adhesion protein (TRAP) candidate vaccines are designed to potently induce effector T cells and so are a departure from earlier malaria vaccines evaluated in the field in terms of their mechanism of action. ME-TRAP vaccines encode a polyepitope string and the TRAP sporozoite antigen. Two vaccine vectors encoding ME-TRAP, plasmid DNA and modified vaccinia virus Ankara (MVA), when used sequentially in a prime-boost immunisation regime, induce high frequencies of effector T cells and partial protection, manifest as delay in time to parasitaemia, in a clinical challenge model. METHODS AND FINDINGS: A total of 372 Gambian men aged 15-45 y were randomised to receive either DNA ME-TRAP followed by MVA ME-TRAP or rabies vaccine (control). Of these men, 296 received three doses of vaccine timed to coincide with the beginning of the transmission season (141 in the DNA/MVA group and 155 in the rabies group) and were followed up. Volunteers were given sulphadoxine/pyrimethamine 2 wk before the final vaccination. Blood smears were collected weekly for 11 wk and whenever a volunteer developed symptoms compatible with malaria during the transmission season. The primary endpoint was time to first infection with asexual P. falciparum. Analysis was per protocol. DNA ME-TRAP and MVA ME-TRAP were safe and well-tolerated. Effector T cell responses to a non-vaccine strain of TRAP were 50-fold higher postvaccination in the malaria vaccine group than in the rabies vaccine group. Vaccine efficacy, adjusted for confounding factors, was 10.3% (95% confidence interval, -22% to +34%; p = 0.49). Incidence of malaria infection decreased with increasing age and was associated with ethnicity. CONCLUSIONS: DNA/MVA heterologous prime-boost vaccination is safe and highly immunogenic for effector T cell induction in a malaria-endemic area. But despite having produced a substantial reduction in liver-stage parasites in challenge studies of non-immune volunteers, this first generation T cell-inducing vaccine was ineffective at reducing the natural infection rate in semi-immune African adults.

Adolescent↗
PubMed2004

A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease.

Many human T-cell responses specific for epitopes in Plasmodium falciparum have been described, but none has yet been shown to be predictive of protection against natural malaria infection. Here we report a peptide-specific T-cell assay that is strongly associated with protection of humans in The Gambia, West Africa, from both malaria infection and disease. The assay detects interferon-gamma-secreting CD4(+) T cells specific for a conserved sequence from the circumsporozoite protein, which binds to many human leukocyte antigen (HLA)-DR types. The correlation was observed using a cultured, rather than an ex vivo, ELISPOT assay that measures central memory-'type T cells rather than activated effector T cells. These findings provide direct evidence for a protective role for CD4(+) T cells in humans, and a precise target for the design of improved vaccines against P. falciparum.

Adolescent↗
PubMed2003

Safety and immunogenicity of DNA/modified vaccinia virus ankara malaria vaccination in African adults.

The present study is an investigation of the safety and immunogenicity of DNA and modified vaccinia virus Ankara (MVA) candidate vaccines, each encoding the malaria DNA sequence multiple epitope-thrombospondin related adhesion protein (ME-TRAP), against Plasmodium falciparum. DNA ME-TRAP and MVA ME-TRAP are safe and immunogenic for effector and memory T cell induction. MVA ME-TRAP, with or without prior DNA ME-TRAP immunization, was more immunogenic and more cross-reactive in malaria-exposed individuals than in malaria-naive individuals, a finding suggesting that recombinant MVA vaccines are particularly promising for the development of a malaria vaccine for exposed populations. Both CD4(+) and CD8(+) T cells were induced by these vaccines.

Adult↗
PubMed2003

Protective efficacy of the RTS,S/AS02 Plasmodium falciparum malaria vaccine is not strain specific.

RTS,S/AS02 is a recombinant protein malaria vaccine that contains a large portion of the C-terminal of the circumsporozoite protein (CSP) sequence of the NF54 isolate of Plasmodium falciparum fused to the hepatitis B virus surface antigen. It has been shown to induce significant protection to challenge infection with a homologous parasite strain in American volunteers. In a recently completed trial in semi-immune Gambian adults, vaccine efficacy against natural infection was 34% (95% confidence interval = 8-53%, P = 0.014) during the malaria season following vaccination. Breakthrough P. falciparum parasites sampled from vaccinated subjects and from controls were genotyped at two polymorphic regions of the csp gene encoding T cell epitopes (csp-th2r and csp-th3r) to determine if the vaccine conferred a strain-specific effect. The overall distribution of csp allelic variants was similar in infections occurring in vaccine and control groups. Also, the mean number of genotypes per infection in the RTS,S/AS02 group was not reduced compared with the controls.

Adolescent↗
PubMedDate not supplied

Malaria.

Malaria is the most important parasitic infection in people, accounting for more than 1 million deaths a year. Malaria has become a priority for the international health community and is now the focus of several new initiatives. Prevention and treatment of malaria could be greatly improved with existing methods if increased financial and labour resources were available. However, new approaches for prevention and treatment are needed. Several new drugs are under development, which are likely to be used in combinations to slow the spread of resistance, but the high cost of treatments would make sustainability difficult. Insecticide-treated bed-nets provide a simple but effective means of preventing malaria, especially with the development of longlasting nets in which insecticide is incorporated into the net fibres. One malaria vaccine, RTS,S/AS02, has shown promise in endemic areas and will shortly enter further trials. Other vaccines are being studied in clinical trials, but it will probably be at least 10 years before a malaria vaccine is ready for widespread use.

Humans↗